The positioning of chromatin within the nucleus plays an important role in gene regulation. The underlying mechanisms are poorly understood, but recent evidence indicates that architectural features such as the nuclear envelope (NE) can control gene expression by defining specific repressive environments. On , Gideon Rechavi and co-workers define the role of a key NE protein, LAP2β, in this process. They find that LAP-2 β acts as a general repressor that can inhibit various transcription factors (e.g. NF-βB, p53 and E2F proteins) in luciferase reporter assays. They also observe that it interacts and colocalizes at the NE with HDAC-3, one of a group of histone deacetylases known to repress transcription by modifying histones. By contrast, LAP-2 β does not interact with the related enzyme HDAC1. The authors go on to demonstrate that the HDAC inhibitor trichostatin A blocks the repressive effect of LAP-2 β and that LAP2 β can induce deacetylation of histone H4 both in vitro and in vivo. Their findings provide valuable insight into the role of the NE in epigenetics and could be particularly significant given the various severe laminopathies that arise from disruption of NE protein function.
